Synthesis and Biological Evaluation of Methylenecyclopropane Analogues of Nucleosides

Germain Obame; Paul Brémond; Christophe Pannecouque; Gérard Audran

doi:10.1055/s-0033-1339311

Synthesis, Table of Contents

Synthesis 2013; 45(18): 2612-2618
DOI: 10.1055/s-0033-1339311

paper

Synthesis and Biological Evaluation of Methylenecyclopropane Analogues of Nucleosides

Germain Obame

^aAix-Marseille Université, CNRS ICR – UMR 7273, 13397 Marseille Cedex 20, France

,

Paul Brémond

^aAix-Marseille Université, CNRS ICR – UMR 7273, 13397 Marseille Cedex 20, France

,

Christophe Pannecouque

^bRega Institute for Medical Research, Katholieke Universiteit Leuven, 10 Minderbroedersstraat, 3000 Leuven, Belgium Fax: +33(4)91288545 Email: g.audran@univ-amu.fr

,

Gérard Audran*

^aAix-Marseille Université, CNRS ICR – UMR 7273, 13397 Marseille Cedex 20, France

› Author Affiliations

Abstract

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Abstract

Starting from a chiral methylenecyclopropane building block, readily obtained by enzymatic desymmetrization of a meso-diol, two types of methylenecyclopropane analogues of nucleosides were synthesized. The first type of nucleosides was obtained from the direct coupling of the chiral building block with 6-chloropurine under Mitsunobu reaction conditions followed by the functionalization of the purine base. The second type of nucleosides featured a Curtius rearrangement as the key step and the uracil heterocycle was then constructed by a linear methodology. These derivatives were evaluated as potential agents against important viral pathogens. None of the new compounds had significant antiviral activity at a concentration of 100 μg/mL, which was the highest concentration tested.

Key words

stereoselective synthesis - Curtius rearrangement - carbocyclic nucleosides - methylenecyclopropane carbonucleosides - antiviral agents

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References

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